DNA Comparison Provides New Clues to Primate Biology

BETHESDA, Md., Thurs., April 12, 2007 - An international consortium of researchers
has published the genome sequence of the rhesus macaque monkey and aligned it
with the chimpanzee and human genomes. Published April 13 in a special section
of the journal Science, the analysis reveals that the three primate species
share about 93 percent of their DNA, yet have some significant differences among
their genes.

In its paper, the Rhesus Macaque Genome Sequence and Analysis Consortium,
supported in part by the National Human Genome Research Institute (NHGRI), one
of the National Institutes of Health (NIH), compared the genome sequences of
rhesus macaque (Macaca mulatta) with that of human (Homo sapiens) and chimp
(Pan troglodytes), the primate most closely related to humans. Four companion
papers that relied on the rhesus sequence also appear in the same issue.

The rhesus genome is the second non-human primate, after the chimp, to have
its genome sequenced and is the first of the Old World monkeys to have its DNA
deciphered.

"The sequencing of the rhesus macaque genome, combined with the availability
of the chimp and human genomes, provides researchers with another powerful tool
to advance our understanding of human biology in health and disease," said
NHGRI Director Francis S. Collins, M.D., Ph.D. "As we build upon the foundation
laid by the Human Genome Project, it has become clear that comparing our genome
with the genomes of other organisms is crucial to identifying what makes the
human genome unique."

The rhesus, because of its response to the simian immunodeficiency virus (SIV),
is widely recognized as the best animal model for human immunodeficiency virus
(HIV) infection. The rhesus genome sequence will
also serve to enhance essential research in neuroscience, behavioral biology,
reproductive physiology, endocrinology and cardiovascular studies. In addition,
the rhesus serves as a valuable model for studying other human infectious diseases
and for vaccine research.

The sequencing of the rhesus genome was conducted at the Baylor College of
Medicine Human Genome Sequencing Center in Houston, the Genome Sequencing Center
at Washington University School of Medicine in St. Louis and the J. Craig Venter
Institute in Rockville, Md., which are part of the NHGRI-supported Large-Scale
Sequencing Research Network. The DNA used in the sequencing was obtained from
a female rhesus macaque at the Southwest National Primate Research Center (NPRC)
in San Antonio, which is supported by the National Center for Research Resources,
part of NIH.

Independent assemblies of the rhesus genome data were carried out at each of
the three sequencing centers using different and complementary approaches and
then combined into a single "melded assembly." In their analysis,
scientists from 35 institutions compared this melded assembly to the reference
sequence of the human genome, a newer unpublished draft sequence of the chimp
genome, the sequence of more than a dozen other more distant species already
in the public databases, the human HapMap, and the Human Gene Mutation Database
that lists known human mutations that lead to genetic disease.

"This study of the rhesus genome is invaluable because it gives researchers
a perspective to observe what has been added or deleted in each primate genome
during evolution of rhesus, chimp, and the human from their common ancestors,"
said Richard Gibbs, Ph.D., director of Baylor College of Medicine's Human Genome
Sequencing Center in Houston and the project leader.

One of the most useful features of the rhesus genome is that it is less closely
related to the human genome than to the chimp genome. This means that important
features that have been conserved in primates over time can be more easily seen
by comparing rhesus to human, than chimp to human.

By adding the rhesus genome to the primate comparison, researchers identified
nearly 200 genes likely to be key players in determining differences among primate
species. These include genes involved in hair formation, immune response, membrane
proteins and sperm-egg fusion. Many of these genes are located in areas of the
primate genome that have been subject to duplication, indicating that having
an extra copy of a gene may enable it to evolve more rapidly and that small
duplications are a key feature of primate evolution.

The analysis also revealed a few instances in which whole families of genes
were radically different in the rhesus, containing more copies of certain genes
than in the chimp or human. These gene families include important immune related
genes, as well as genes with functions not yet fully known.

In addition to comparing the rhesus with the chimp and human genomes, the
group also studied genetic variation in macaque populations, and developed a
set of "single nucleotide polymorphisms" or SNPs (single base DNA
differences) that can be used for future analysis of inheritance of biomedically
important traits in rhesus. The rhesus genomic DNA samples used for these studies
were contributed by the California NPRC, Oregon NPRC, Southwest NPRC and Yerkes
NPRC. This advance in macaque genetics will enhance the use of macaques for
the study of genetic diseases of man.

The rhesus study is part of an ongoing program to analyze primate genomes.
Other primate genomes underway include the marmoset, gibbon and gorilla. Researchers
at the Baylor Center and the Washington University Genome Center completed the
raw sequence for the orangutan and marmoset genomes early this year, and Washington
University has deposited the assemblies at the Genome Sequencing Center [genome.wustl.edu]. Researchers
plan to analyze the orangutan and marmoset genomes and compare them with the
other primates over the summer.

The chimp, orangutan and human genome sequences, along with those of a wide
range of other organisms such as mouse, rat, dog, cow, honey bee, roundworm
and yeast, can be accessed through the following public genome browsers: GenBank
(www.ncbi.nih.gov/Genbank) at NIH's National Center for Biotechnology Information
(NCBI); the UCSC Genome Browser (www.genome.ucsc.edu) at the University of California
at Santa Cruz; the Ensembl Genome Browser (www.ensembl.org) at the Wellcome
Trust Sanger Institute and the EMBL-European Bioinformatics Institute; the DNA
Data Bank of Japan (www.ddbj.nig.ac.jp); and EMBL-Bank, (www.ebi.ac.uk/embl/index.html)
at the European Molecular Biology Laboratory's Nucleotide Sequence Database.

NHGRI is one of 27 institutes and centers at the NIH, an agency of the Department
of Health and Human Services. The NHGRI Division of Extramural Research supports
grants for research and for training and career development at sites nationwide.
Additional information about NHGRI can be found at its Web site, www.genome.gov.

The National Institutes of Health - "The Nation's Medical Research Agency"
- includes 27 institutes and centers, and is a component of the U.S. Department
of Health and Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases. For more,
visit www.nih.gov.